ulonivirine (MK-8507) / Merck (MSD) - LARVOL DELTA

A Clinical Study of Islatravir and Ulonivirine for People With HIV-1 Who Have Not Been Treated Before (MK-8591B-062) (clinicaltrials.gov) - P2/3 | N=570 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P2/3 trial • Human Immunodeficiency Virus • Infectious Disease

A Study of Islatravir (ISL) and Ulonivirine (ULO) Once Weekly (QW) in Virologically Suppressed Adults With Human Immunodeficiency Virus Type 1 (HIV-1) (MK-8591B-060) (clinicaltrials.gov) - P2 | N=150 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Sep 2027 ➔ Sep 2031

Trial completion date • Human Immunodeficiency Virus • Infectious Disease

An Open-Label Phase 1 Study to Evaluate the Effect of Multiple Doses of Rifabutin on the Single-Dose Pharmacokinetics of Ulonivirine in Adults without HIV (IDWeek 2025) - No abstract available

Clinical • P1 data • PK/PD data • Human Immunodeficiency Virus • Infectious Disease

A double-blind, active-controlled, phase 2b study to evaluate the efficacy and safety of ulonivirine in combination with islatravir in virologically suppressed adults living with HIV-1 (IAS-HIV 2025) - P2 | "This double-blind, phase 2b trial evaluated the efficacy and safety of ISL+ULO QW in virologically suppressed adults living with HIV-1 (MK-8591-013; NCT04564547). Participants without known NNRTI resistance who were virologically suppressed for =6 months on bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), were randomized (1:1:1:1) to receive ISL 20 mg plus ULO (100, 200, or 400 mg) QW, or remain on BIC/FTC/TAF once-daily. ISL+ULO showed efficacy in maintaining viral suppression through Week 24. Consistent with previous studies of ISL, decreases in TLC and CD4+ counts were observed with ISL 20 mg + ULO QW followed by a trend to recovery after discontinuation. Development of ISL 2 mg + ULO QW is ongoing."

Clinical • Combination therapy • P2b data • Human Immunodeficiency Virus • Infectious Disease • CD4

A Study of Islatravir (ISL) and Ulonivirine (ULO) Once Weekly (QW) in Virologically Suppressed Adults With Human Immunodeficiency Virus Type 1 (HIV-1) (MK-8591B-060) (clinicaltrials.gov) - P2 | N=150 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Human Immunodeficiency Virus • Infectious Disease

Phase 2 once-weekly dose optimization for ulonivirine in combination with Islatravir 2 mg (IAS-HIV 2025) - P3 | "ULO data from Phase 1 and the previous Phase 2 studies were used to predict a safe and efficacious Phase 2 ULO dose to be combined with ISL 2 mg QW, which is the lower ISL dose used in ongoing clinical trials in combination with oral lenacapavir [NCT06630286; NCT06630299] and is expected to be safe and efficacious. Reduction in viral load (measured as log10 plasma HIV-1 RNA copies/mL]) and ULO pharmacokinetics (PK) from a Phase 1b study where treatment-naïve participants living with HIV-1 received single oral doses of ULO (40, 80, or 600 mg) were used to establish a wild-type (WT) efficacy PK threshold. Dose selection factors weighed PK coverage and virological efficacy. Weekly 200 mg ULO in combination with ISL 2 mg was selected for Phase 2 for continued clinical development."

Combination therapy • P2 data • Human Immunodeficiency Virus • Infectious Disease

An open-label Phase 1 study to evaluate drug interactions between multiple weekly doses of ulonivirine (MK-8507) and single doses of islatravir in adults without HIV (IAS-HIV 2025) - "No clinically meaningful DDI was observed when ULO and ISL were co-administered."

Clinical • P1 data • Human Immunodeficiency Virus • Infectious Disease • CD4

A double-blind, placebo-controlled, Phase 1 study to evaluate extended multiple dosing of ulonivirine (MK-8507) in adults without HIV (IAS-HIV 2025) - "BACKGROUND: Ulonivirine (ULO, MK-8507), an NNRTI with a favorable safety profile and pharmacokinetic properties that support once-weekly (QW) dosing, is in development in combination with islatravir (ISL) for the treatment of HIV-1. ULO 200 mg QW demonstrated an AE profile similar to that of placebo and did not decrease total lymphocyte or CD4+ T-cell counts to a clinically significant degree in adults without HIV."

Clinical • P1 data • Human Immunodeficiency Virus • Infectious Disease • CD4

A Study of Islatravir (ISL) and Ulonivirine (ULO) Once Weekly (QW) in Virologically Suppressed Adults With Human Immunodeficiency Virus Type 1 (HIV-1) (MK-8591B-060) (clinicaltrials.gov) - P2 | N=150 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease

A Study of Islatravir (ISL) and Ulonivirine (ULO) Once Weekly (QW) in Virologically Suppressed Adults With Human Immunodeficiency Virus Type 1 (HIV-1) (MK-8591B-060) (clinicaltrials.gov) - P2 | N=150 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P2 trial • Human Immunodeficiency Virus • Infectious Disease

Ulonivirine (MK-8507) in Participants With Mild or Moderate Hepatic Impairment (MK-8507-014) (clinicaltrials.gov) - P1 | N=22 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Sep 2025 ➔ Sep 2026 | Trial primary completion date: Sep 2025 ➔ Sep 2026

Trial completion date • Trial primary completion date • Hepatitis C • Hepatology • Liver Failure

Dose Ranging, Switch Study of Islatravir (ISL) and Ulonivirine (MK-8507) Once-Weekly in Virologically-Suppressed Adults With Human Immunodeficiency Virus Type 1 (HIV-1) [MK-8591-013] (clinicaltrials.gov) - P2 | N=161 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease • CD4

Dose Ranging, Switch Study of Islatravir (ISL) and Ulonivirine (MK-8507) Once-Weekly in Virologically-Suppressed Adults With Human Immunodeficiency Virus Type 1 (HIV-1) [MK-8591-013] (clinicaltrials.gov) - P2 | N=161 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Dec 2024 ➔ Mar 2025 | Trial primary completion date: Dec 2024 ➔ Mar 2025

Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • CD4

A Study of MK-8507 and Islatravir (MK-8591) in Healthy Adult Participants (MK-8507-016) (clinicaltrials.gov) - P1 | N=36 | Completed | Sponsor: Merck Sharp & Dohme LLC

New P1 trial

Ulonivirine (MK-8507) in Participants With Mild or Moderate Hepatic Impairment (MK-8507-014) (clinicaltrials.gov) - P1 | N=22 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Apr 2025 ➔ Sep 2025 | Trial primary completion date: Apr 2025 ➔ Sep 2025

Trial completion date • Trial primary completion date • Hepatitis C • Hepatology • Liver Failure

Dose Ranging, Switch Study of Islatravir (ISL) and Ulonivirine (MK-8507) Once-Weekly in Virologically-Suppressed Adults With Human Immunodeficiency Virus Type 1 (HIV-1) [MK-8591-013] (clinicaltrials.gov) - P2 | N=161 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Phase classification: P2b ➔ P2 | Trial completion date: Dec 2023 ➔ Sep 2024 | Trial primary completion date: Dec 2023 ➔ Sep 2024

Phase classification • Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • CD4

Ulonivirine (MK-8507) in Participants With Mild or Moderate Hepatic Impairment (MK-8507-014) (clinicaltrials.gov) - P1 | N=22 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Oct 2025 ➔ Apr 2025 | Trial primary completion date: Oct 2025 ➔ Apr 2025

Trial completion date • Trial primary completion date • Hepatitis C • Hepatology • Liver Failure

Ulonivirine (MK-8507) in Participants With Mild or Moderate Hepatic Impairment (MK-8507-014) (clinicaltrials.gov) - P1 | N=22 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Feb 2024 ➔ Oct 2025 | Trial primary completion date: Feb 2024 ➔ Oct 2025

Trial completion date • Trial primary completion date • Hepatitis C • Hepatology • Liver Failure

Dose Ranging, Switch Study of Islatravir (ISL) and Ulonivirine (MK-8507) Once-Weekly in Virologically-Suppressed Adults With Human Immunodeficiency Virus Type 1 (HIV-1) [MK-8591-013] (clinicaltrials.gov) - P2b | N=161 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Jun 2023 ➔ Dec 2023 | Trial primary completion date: Jun 2023 ➔ Dec 2023

Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • CD4

MK-8507 in Participants With Mild or Moderate Hepatic Impairment (MK-8507-014) (clinicaltrials.gov) - P1 | N=22 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Jan 2023 ➔ Feb 2024 | Trial primary completion date: Jan 2023 ➔ Feb 2024

Trial completion date • Trial primary completion date • Hepatitis C • Hepatology • Liver Failure

Approved HIV reverse transcriptase inhibitors in the past decade. (PubMed, Acta Pharm Sin B) - "Here, we provide a comprehensive review of RT inhibitors (tenofovir alafenamide, rilpivirine, doravirine, dapivirine, azvudine and elsulfavirine) approved in the past decade, regarding their drug discovery, pharmacology, and clinical efficacy in randomized controlled trials. Novel RT inhibitors such as islatravir, MK-8504, MK-8507, MK8583, IQP-0528, and MIV-150 will be also highlighted. Future development may focus on the new generation of novel antiretroviral inhibitors with higher bioavailability, longer elimination half-life, more favorable side-effect profiles, fewer drug-drug interactions, and higher activities against circulating drug-resistant strains."

Journal • Review • Human Immunodeficiency Virus • Immunology • Infectious Disease

Dose Ranging, Switch Study of Islatravir (ISL) and MK-8507 Once-Weekly in Virologically-Suppressed Adults With Human Immunodeficiency Virus Type 1 (HIV-1) [MK-8591-013] (clinicaltrials.gov) - P2b | N=161 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Jun 2024 ➔ Jun 2023

Trial completion date • Human Immunodeficiency Virus • Immunology • Infectious Disease • CD4

Dose Ranging, Switch Study of Islatravir (ISL) and MK-8507 Once-Weekly in Virologically-Suppressed Adults With Human Immunodeficiency Virus Type 1 (HIV-1) [MK-8591-013] (clinicaltrials.gov) - P2b | N=161 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial primary completion date: Jun 2022 ➔ Jun 2023

Trial primary completion date • Human Immunodeficiency Virus • Immunology • Infectious Disease • CD4

MK-8507 in Participants With Mild or Moderate Hepatic Impairment (MK-8507-014) (clinicaltrials.gov) - P1 | N=22 | Not yet recruiting | Sponsor: Merck Sharp & Dohme Corp. | Trial completion date: May 2022 ➔ Jan 2023 | Initiation date: Nov 2021 ➔ Jul 2022 | Trial primary completion date: May 2022 ➔ Jan 2023

Trial completion date • Trial initiation date • Trial primary completion date • Hepatitis C • Hepatology • Liver Failure

MK-8507 in Participants With Mild or Moderate Hepatic Impairment (MK-8507-014) (clinicaltrials.gov) - P1; N=22; Not yet recruiting; Sponsor: Merck Sharp & Dohme Corp.

Clinical • New P1 trial • Hepatitis C • Hepatology • Liver Failure